Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Nanocompósitos magnéticos para concentração/remoção de contaminantes de águas / Magnetic adsorbent nanocomposites for water treatment

Zeólitas e carvão ativado são materiais eficazes para o tratamento de efluentes devido a sua grande área superficial e possibilidades de funcionalização, que permitem o desenvolvimento de novos materiais derivados visando a processos de concentração/remoção de contaminantes, por exemplo, em águas. A preparação de nanocompósitos magnéticos e sua aplicação na remoção seletiva de poluentes em meio aquoso tornou-se viável devido as interações distintas que ocorrem entre zeólita e carvão ativado com compostos orgânicos, íons metálicos e compostos nitrogenados. Assim, novos materiais voltados para sistemas de tratamento de águas residuais e monitoramento ambiental foram desenvolvidos com base em materiais bem estabelecidos. Os nanocompósitos foram caracterizados estrutural e morfologicamente por técnicas de microscopia eletrônica de varredura, termogravimetria, espectroscopia no infravermelho, espalhamento de luz, difração de raios x, bem como suas capacidades de adsorção. Foi avaliado também a viabilidade de aplicações em métodos analíticos, como pré-concentração por extração em fase sólida magnética (M-SPE), e, para tratamento de efluentes em amostras reais. Contaminação por cromo (VI), outras espécies potencialmente tóxicas e amônio foram removidos de águas residuais, gerando produtos tratados com níveis de contaminantes suficientemente baixos para atenderem as recomendações da EPA (Environmental Protection Agency) e CONAMA (Conselho Nacional do Meio Ambiente), permitindo seu descarte na natureza. Os materiais demonstraram ser adequados para pré-concentração rápida, eficiente, economicamente competitiva e ambientalmente amigável de amostras por M-SPE para quantificação analítica de espécies orgânicas ou inorgânicas, por técnicas analíticas convencionais. Assim, foi demonstrado a possibilidade de determinação simultânea de elementos potencialmente tóxicos e de outros cátions metálicos em concentrações traço (ppb), diretamente no material compósito magnético, por espectroscopia de fluorescência de raios X de energia dispersiva (EDX), além da quantificação de traços de compostos orgânicos semi-voláteis por cromatografia emfase gasosa com detector por espectrometria de massas, aumentando a sensibilidade para além do limite nominal de detecção por essas técnicas

Zeolites and activated carbon are effective materials for the treatment of effluents due to their large surface area and functionalisation possibilities, which allow the development of new derived materials aiming at the concentration/removal of contaminants from water, for example. The preparation of magnetic nanocomposites and their application in the selective removal of pollutants in aqueous media has become feasible due to the distinct interactions that occur between zeolite and activated carbon with organic compounds, metal ions and nitrogen compounds. Thus, new materials for wastewater treatment and environmental monitoring systems were developed based on well-established materials. The nanocomposites were structural and morphologically characterized by scanning electron microscopy, thermogravimetry, infrared spectroscopy, light scattering, x-ray diffraction, as well as their adsorption capacities, viability of applications in analytical methods such as preconcentration by extraction in magnetic solid phase, M-SPE, were evaluated, and the composite materials Cmag and Zmag applied for treatment of real samples. Chromium (VI) contamination, heavy metal cations and ammonium were removed from wastewater, generating treated products with levels of contaminants low enough to meet the EPA and CONAMA recommendations, allowing their disposal in the wild. The materials have been shown to be suitable for rapid, efficient, economically competitive and environmentally friendly preconcentration of samples per M-SPE for analytical quantification of organic or inorganic species by conventional analytical techniques. Thus, it was demonstrated the possibility of simultaneous analysis of heavy metals and other metal cations in trace concentrations (ppb), directly in the magnetic composite material, by dispersive energy X-ray fluorescence spectroscopy (EDX), in addition to the quantification of traces of volatile organic compounds (VOC) by gas chromatography with mass spectrometry detector, increasing the sensitivity beyond the nominal limit of detection by these techniques

Physicochemical, Thermal, Structural and Pasting Properties of Unconventional Starches from Ginger (Zingiber officinale) and White Yam (Dioscorea sp)

Abstract Ginger and white yam starches were investigated and compared with maize starch. Proximal composition, thermogravimetry, differential scanning calorimetry, microscopy, colourimetry, X-ray powder diffractometry and pasting profile were analysed. The unconventional starches presented higher protein and ash contents than the maize starch, that had the highest thermal stability. Higher gelatinisation temperatures were reported for ginger starch, and the enthalpy of the unconventional starches were similar. The maize starch presented the lowest gelatinisation values. For the corn starch the granules were polygonal and smaller than the unconventional starches, and oval shapes and larger diameters were found for the ginger and yam starches. The unconventional starches presented less brightness and a greater tendency to red and yellow. The maize and ginger starches had A-type diffraction patterns, while the white yam starch had a C-type pattern. The highest relative crystallinity was observed for the ginger starch and there were small differences between the yam and maize starches. Higher peak viscosity and final viscosity and lower pasting temperature were observed for the yam starch. Ginger starch showed the highest shear and stability of heating glue, so may be used in products processed under high temperatures; and yam starch can be used in acidic foods that require high viscosities.

Rufinamide: Crystal structure elucidation and solid state characterization.

Rufinamide (R) is a triazole derivative approved for the management of partial seizures and seizures associated with Lennox-Gastaut Syndrome, in November 2007. Crystal structure, solid state characterization, drug-excipient compatibility and solubility play a pivotal role in formulation development. This work deals with the crystal structure elucidation of R by single crystal X-ray diffraction and solid state characterization by thermal, spectroscopic and crystallographic techniques. Drug- excipient compatibility was assessed by differential scanning calorimetry (DSC). New RP-HPLC method for quantification of R was developed with improved retention time. Solubility and dissolution of drug in different media was determined. Additionally, the flow behavior of the drug was evaluated by measuring Carr's index and Hausner's ratio, while the compressibility behavior was studied using Well's protocol. R crystallized from dimethylformamide (R-DMF) was utilized for single crystal analysis. The drug crystallized in triclinic crystal system with P-1 space group. Asymmetric unit cell consists of two molecules of R held by intermolecular hydrogen bond (connected by NH⋯O, which forms the catemeric chain). Analytical outcomes from DSC, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD) revealed that the drug was present in pure crystalline form and was devoid of any polymorphic or pseudopolymorphic impurities. Influence of pH on the solubility and dissolution of R-DMF was found to be insignificant. The drug exhibited poor aqueous solubility, which was improved nearly 4.6 fold with the addition of 2% sodium lauryl sulphate (SLS). The drug exhibits poor flow and elastic compression nature. Excipients such as poly ethylene glycol (PEG) 8000, SLS, lactose monohydrate, starch and Hydroxypropyl methylcellulose (HPMC) E15 were incompatible with R-DMF as identified by thermal analysis. It is envisaged that these information regarding solid state properties of R-DMF would aid in identifying a logical path for formulation development.

Pyrolysis of tyre powder using microwave thermogravimetric analysis: Effect of microwave power.

The pyrolytic characteristics of tyre powder treated under different microwave powers (300, 500, and 700 W) were studied via microwave thermogravimetric analysis. The product yields at different power levels were studied, along with comparative analysis of microwave pyrolysis and conventional pyrolysis. The feedstock underwent preheating, intense pyrolysis, and final pyrolysis in sequence. The main and secondary weight loss peaks observed during the intense pyrolysis stage were attributed to the decomposition of natural rubbers and synthetic rubbers, respectively. The total mass loss rates, bulk temperatures, and maximum temperatures were distinctively higher at higher powers. However, the maximum mass loss rate (0.005 s-1), the highest yields of liquid product (53%), and the minimum yields of residual solid samples (43.83%) were obtained at 500 W. Compared with conventional pyrolysis, microwave pyrolysis exhibited significantly different behaviour with faster reaction rates, which can decrease the decomposition temperatures of both natural and synthetic rubber by approximately 110 °C-140 °C.

VISTA: A µ-Thermogravimeter for Investigation of Volatile Compounds in Planetary Environments.

This paper presents the VISTA (Volatile In Situ Thermogravimetry Analyser) instrument, conceived to perform planetary in-situ measurements. VISTA can detect and quantify the presence of volatile compounds of astrobiological interest, such as water and organics, in planetary samples. These measurements can be particularly relevant when performed on primitive asteroids or comets, or on targets of potential astrobiological interest such as Mars or Jupiter's satellite Europa. VISTA is based on a micro-thermogravimetry technique, widely used in different environments to study absorption and sublimation processes. The instrument core is a piezoelectric crystal microbalance, whose frequency variations are affected by variations of the mass of the deposited sample, due to chemical processes such as sublimation, condensation or absorption/desorption. The low mass (i.e. 40 g), the low volume (less than 10 cm(3)) and the low power (less than 1 W) required makes this kind of instrument very suitable for space missions. This paper discusses the planetary applications of VISTA, and shows the calibration operations performed on the breadboard, as well as the performance tests which demonstrate the capability of the breadboard to characterize volatile compounds of planetary interests.

Development of a modified independent parallel reactions kinetic model and comparison with the distributed activation energy model for the pyrolysis of a wide variety of biomass fuels.

The pyrolysis of six waste biomass samples was studied and the fuels were kinetically evaluated. A modified independent parallel reactions scheme (IPR) and a distributed activation energy model (DAEM) were developed and their validity was assessed and compared by checking their accuracy of fitting the experimental results, as well as their prediction capability in different experimental conditions. The pyrolysis experiments were carried out in a thermogravimetric analyzer and a fitting procedure, based on least squares minimization, was performed simultaneously at different experimental conditions. A modification of the IPR model, considering dependence of the pre-exponential factor on heating rate, was proved to give better fit results for the same number of tuned kinetic parameters, comparing to the known IPR model and very good prediction results for stepwise experiments. Fit of calculated data to the experimental ones using the developed DAEM model was also proved to be very good.

Thermogravimetric investigation on characteristic of biomass combustion under the effect of organic calcium compounds.

Experiments were conducted in a thermogravimetric analyzer to investigate thermal behavior of different organic calcium compounds (OCCs) and its blended fuels with three kinds of biomass. The effectiveness of synthesized method for OCC was assessed by the pyrolysis test. Effect of the mole ratio of calcium to sulfur on co-combustion characteristics was studied. Results indicated that preparation method of modified calcium acetate (MCA) had high precision and accuracy. Co-combustion characteristic of OCCs blended with biomass was controlled by OCCs' additive amount and the content of volatile matter which is mainly composed of small hydrocarbon molecules. Combustion performance indexes for peanut shell and wheat straw impregnated by OCCs were improved, however, an inverse trend was found for rice husk because of lower additive amount of OCCs. The blended fuel show higher combustion performance indexes compared with combustion of individual biomass, and these indexes decrease with increases of Ca/S ratio.

Comparative study on pyrolysis of lignocellulosic and algal biomass using a thermogravimetric and a fixed-bed reactor.

Pyrolysis characteristics of four algal and lignocellulosic biomass samples were studied by using a thermogravimetric analyzer (TGA) and a fixed-bed reactor. The effects of pyrolysis temperature and biomass type on the yield and composition of pyrolysis products were investigated. The average activation energy for pyrolysis of biomass samples by FWO and KAS methods in this study were in the range of 211.09-291.19kJ/mol. CO2 was the main gas component in the early stage of pyrolysis, whereas H2 and CH4 concentrations increased with increasing pyrolysis temperature. Bio-oil from Chlorellavulgaris showed higher content of nitrogen containing compounds compared to lignocellulosic biomass. The concentration of aromatic organic compounds such as phenol and its derivatives were increased with increasing pyrolysis temperature up to 700°C. FTIR analysis results showed that with increasing pyrolysis temperature, the concentration of OH, CH, CO, OCH3, and CO functional groups in char decreased sharply.

Co-pyrolysis of pine sawdust and lignite in a thermogravimetric analyzer and a fixed-bed reactor.

Co-pyrolysis characteristics of lignite and pine sawdust were studied in a TGA and a fixed-bed reactor. The effects of pyrolysis temperature and blending ratio on the yield and composition of pyrolysis products (gas, tar, and char) were investigated. TGA experiments showed that pine sawdust decomposition took place at lower temperatures compared to lignite. With increasing the pine sawdust content in the blend, the DTG peaks shifted towards lower temperatures due to synergetic effect. In fixed-bed experiments, the synergetic effect increased the yield of volatile matter compared to the calculated values. The major gases released at low temperatures were CO2 and CO. However, hydrogen was the primary gaseous product at higher temperatures. During co-pyrolysis, concentrations of benzene, naphthalene, and hydrocarbons in the tar decreased, accompanied by an increase in phenols and guaiacol concentrations. With increasing pyrolysis temperature, the OH, aliphatic CH, CO, and CO functional groups in char decomposed substantially.

Miniature quartz crystal-resonator-based thermogravimetric detector.

In this work, a new design for a microheater combined with a quartz crystal microbalance (QCM) array for thermogravimetric analysis is presented. Each QCM consists of two electrodes to excite thickness-shear-mode vibrations and one microheater to increase the temperature on the crystal backside. In addition, all the electrode pads are patterned on the crystal backside, making the design of the QCM compact and user-friendly. Finally, the proposed QCM array was employed to separate ethanol from methanol. This was successfully achieved via thermal desorption spectra calculated by differentiating the frequency changes.

Pyrolysis characteristics and kinetics of aquatic biomass using thermogravimetric analyzer.

The differences in pyrolysis process of three species of aquatic biomass (microalgae, macroalgae and duckweed) were investigated by thermogravimetric analysis (TGA). Three stages were observed during the pyrolysis process and the main decomposition stage could be divided further into three zones. The pyrolysis characteristics of various biomasses were different at each zone, which could be attributed to the differences in their components. A stepwise procedure based on iso-conversional and master-plots methods was used for the kinetic and mechanism analysis of the main decomposition stage. The calculation results based on the kinetic model was in good agreement with the experimental data of weight loss, and each biomass had an increasing activation energy of 118.35-156.13 kJ/mol, 171.85-186.46 kJ/mol and 258.51-268.71 kJ/mol in zone 1, 2 and 3, respectively. This study compares the pyrolysis behavior of various aquatic biomasses and provides basis for further applications of the biomass thermochemical conversion.

Temperature-dependent deliquescence relative humidities and water activities using humidity controlled thermogravimetric analysis with application to malonic acid.

We utilize a new experimental technique, humidity-controlled thermogravimetric analysis (HTGA), to determine temperature-dependent deliquescence relative humidities (DRH) and to determine the equilibrium concentration of a solution at a given temperature and relative humidity. To that end, we have investigated the malonic acid/water system determining the DRH and concentration/RH relationship in the temperature range 303-278 K. Excellent agreement is found with literature values for the DRH of malonic acid as a function of temperature and for the concentration/RH relationship at several temperatures. Thus, we extend the DRH and concentration/RH relationship to a broader temperature range and are using the HTGA experiments to investigate other organic acids.

Rapid comprehensive characterization of crude oils by thermogravimetry coupled to fast modulated gas chromatography-single photon ionization time-of-flight mass spectrometry.

Comprehensive multi-dimensional hyphenation of a thermogravimetry device (i.e. a thermobalance) to gas chromatography and single photon ionization-time-of-flight mass spectrometry (TG-GC×SPI-MS) has been used to investigate two crude oil samples of different geographical origin. The source of the applied vacuum ultraviolet radiation is an electron beam pumped rare gas excimer lamp (EBEL). The soft photoionization favors the formation of molecular ions. Introduction of a fast, rapidly modulated gas chromatographic separation step in comparison with solely TG-SPI-MS enables strongly enhanced detection especially with such highly complex organic matrices as crude oil. In contrast with former TG-SPI-MS measurements, separation and identification of overlying substances is possible because of different GC retention times. The specific contribution of isobaric compounds to one mass signal is determined for alkanes, naphthalenes, alkylated benzenes, and other compounds.

Preparation, chromatographic evaluation and comparison between linear peptide- and cyclopeptide-bonded stationary phases.

In this paper, linear and cyclic tetrapeptide bonded stationary phases, were synthesized by the solid-phase synthesis method. Each amino acid coupling step was monitored by the ninhydrin test using UV/visible spectrophotometry. The proposed materials were characterized by UV spectroscopy, Fourier transform infrared spectroscopy, elemental analysis and thermogravimetric analysis, which proved the successful immobilization of tetrapeptide on the silica support. The cyclopeptide stationary phase displayed mixed-mode behavior and had the size selectivity for polycyclic aromatic hydrocarbon such as anthracene, while the linear peptide stationary phase only exhibited typical hydrophilic interaction chromatography (HILIC) characteristics and was more hydrophilic under the same mobile phase condition. Retention behaviors of polar compounds on the two stationary phases were studied through varying column temperature, the water content, pH and ionic strength in mobile phase. Applications in the separation of the mixture of nucleosides, sulfa compounds, organic acids and isomers of substituted benzoic acid compounds were demonstrated.

Considerations in determination of residual moisture in lyophilized demineralized bone matrix: the role of residual moisture analyzers.

The objective of this study is to determine whether a residual moisture analyzer (RMA) can be an acceptable instrument for measuring the residual moisture in lyophilized demineralized bone matrix (DBM). Instruments from two different manufacturers with differing configurations and controls were compared: the Ohaus MB45 and Arizona Instrument MAX4000XL. The effects of various factors such as test temperature, drying profile, end point criteria, lift compensation, chamber configuration, and rehydration on residual moisture (RM) are examined. The performance of the RMAs is based on their ability to reproduce RM results obtained by the current standard gravimetric method. RMAs provide reliable, accurate and reproducible results in a number of industries that rely on the determination of RM. We hypothesize that RMAs are suitable for measuring RM in DBM and provide validation study data with optimized settings for these two instruments. Potentially, such studies will provide justification for allowance of this methodology as an acceptable alternative to the current gravimetric method allowed by American Association of Tissue Banks Standards.

Correlation of thermal analysis and pyrolysis coupled to GC-MS in the characterization of tacrolimus.

In recent years, thermal analysis has assumed major role in the pharmaceutical industry because it can be used to evaluate the stability both in the control of raw materials and the finished product, having employment potential in the development and characterization of new products and assessment processes. Tacrolimus (TCR) is a macrolide lactone with potent immunosuppressive activity. The purpose of this study was to characterize tacrolimus raw material using Thermal analysis and Pyrolysis coupled to Gas chromatography-Mass spectrometry (Pyr-GC-MS). It was analyzed four samples of tacrolimus named TCR A, B, C and D. Thermal analysis experiments was performed in Shimadzu equipment, under nitrogen and synthetic air atmosphere in different heating rate. Pyrolysis analysis was conducted in isothermal conditions of 300°C and 400°C coupled to GC-MS, in which the mass spectrometer was operated in scan mode to detect ions in the range of mass of m/z 25-900. The thermal studies by DSC, DTA and DSC-Photovisual showed desolvation process for all tacrolimus raw materials and TG-dynamical demonstrated two pseudo-polymorphic forms (monohydrate and sesquihydrate) of tacrolimus. It was observed good correlation between the stoichiometric mass losses of the TG-dynamical and identification of product ion in Pyr-GC/MS technique. It was possible to correlate the five pyrolytic product ions with the Ozawa kinetic analysis from the thermal decomposition of TG-dynamical. The thermal studies (DSC, DSC-Photovisual, DTA and TG-dynamical) were applied in the thermal characterization of the raw materials of tacrolimus which showed pseudo-polymorphic forms, which must be monitored by pharmaceutical industry, avoiding future problems in pharmaceutical process, chemical stability and bioavailability of the tacrolimus product.

Measurement of thermodiffusion coefficient of hydrocarbon binary mixtures under pressure with the thermogravitational technique.

It was designed and constructed a new thermogravitational column able to operate at high pressures (up to 50 MPa). This new thermogravitational column is of the cylindrical type with closed ends. It is made of stainless steel. The length of the column is 0.5 m and the gap between its two walls is variable. First, the column was validated at atmospheric pressure by means of measurements of the thermodiffusion coefficient of well-known binary mixtures. Then, this new thermogravitational column was used to measure the thermodiffusion coefficient of the binary mixtures 1,2,3,4-tetrahydronaphtalene/isobutylbenzene, 1,2,3,4-tetrahydronaphtalene/n-dodecane, and isobutylbenzene/n-dodecane at high pressures and within the pressure range between 0.1 and 20 MPa at a mean temperature of 25 °C. We have found a linear dependence between the thermodiffusion coefficient and the pressure.

Combustion behaviours of tobacco stem in a thermogravimetric analyser and a pilot-scale fluidized bed reactor.

Despite its abundant supply, tobacco stem has not been exploited as an energy source in large scale. This study investigates the combustion behaviours of tobacco stem in a thermogravimetric analyser (TGA) and a pilot-scale fluidized bed (FB). Combustion characteristics, including ignition and burnout index, and combustion reaction kinetics were studied. Experiments in the FB investigated the effects of different operating conditions, such as primary air flow, secondary air flow and feeding rates, on the bed temperature profiles and combustion efficiency. Two kinds of bed materials cinder and silica sand were used in FB and the effect of bed materials on agglomeration was studied. The results indicated that tobacco stem combustion worked well in the FB. When operation condition was properly set, the tobacco stem combustion efficiency reached 94%. In addition, compared to silica sand, cinder could inhibit agglomeration during combustion because of its high aluminium content.

Application of lag-k autocorrelation coefficient and the TGA signals approach to detecting and quantifying adulterations of extra virgin olive oil with inferior edible oils.

The combination of lag-k autocorrelation coefficients (LCCs) and thermogravimetric analyzer (TGA) equipment is defined here as a tool to detect and quantify adulterations of extra virgin olive oil (EVOO) with refined olive (ROO), refined olive pomace (ROPO), sunflower (SO) or corn (CO) oils, when the adulterating agents concentration are less than 14%. The LCC is calculated from TGA scans of adulterated EVOO samples. Then, the standardized skewness of this coefficient has been applied to classify pure and adulterated samples of EVOO. In addition, this chaotic parameter has also been used to quantify the concentration of adulterant agents, by using successful linear correlation of LCCs and ROO, ROPO, SO or CO in 462 EVOO adulterated samples. In the case of detection, more than 82% of adulterated samples have been correctly classified. In the case of quantification of adulterant concentration, by an external validation process, the LCC/TGA approach estimates the adulterant agents concentration with a mean correlation coefficient (estimated versus real adulterant agent concentration) greater than 0.90 and a mean square error less than 4.9%.